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. Author manuscript; available in PMC: 2020 Feb 1.
Published in final edited form as: Chembiochem. 2018 Dec 27;20(3):394–407. doi: 10.1002/cbic.201800593

Table 3.

Exploration of phenylsubstituents in 2 and their modulatory effect on DGC activity.

graphic file with name nihms-1019449-t0058.jpg
compd R1 R2 IC50 AC50 ±
SD [μM]a 		Hill coeff b % Activity
ESIc
Negative allosteric modulators
2 2-CH3, 5-CH3 4-Morpholine 6.4 ± 0.5 1.36 ± 0.13 31.4 ± 1.3
2a 2-CH3, 4-CH3 4-Morpholine 11.7 ± 1.8 2.01 ± 0.08 69.8 ± 0.7
2c H H 10.6 ± 0.8 2.45 ± 0.34 38.6 ± 2.1
2d 4-CH3 4-Morpholine 207.0 ± 77.8 2.42 ± 1.35 42.2 ± 9.3
2e 2-CH3 4-Morpholine 2.2 ± 0.5 2.34 ± 1.04 63.3 ± 8.5
2f 2-CH3, 5-CH3 3-COCH3 127.3 ± 0.9 1.29 ± 0.10 5.9 ± 0.4
2g H 4-NHCOCH3 620.3 ± 77.2 1.19 ± 0.10 8.3 ± 2.5
2h 4-OCH3 4-NHCO(C3H5) 271.1 ± 13.9 0.96 ± 0.07 1.2 ± 0.0
2i H 4-N(CH3)2 4.4 ± 2.2 2.05 ± 0.12 92.2 ± 0.6
Silent allosteric modulator
2j H 4-Morpholine 12.1 ± 5.2 1.99 ± 0.04 95.5 ± 0.1
Positive allosteric modulators
2k H 2-Morpholine 69.9 ± 5.8 2.87 ± 0.61 172.6 ± 2.4
2l 4-OCH3 2-Morpholine 46.8 ± 3.4 2.84 ± 0.46 167.3 ± 2.2
2m H 3-Sulfonyl-morpholine 25.0 ± 5.3 2.06 ± 0.15 142.0 ± 1.4
2n 4-tBu 2-Hydroxyl, 5-Sulfonylmorpholine 25.4 ± 3.5 2.08 ± 0.51 146.5 ± 4.4
2b H 2-OCH3, 5-Sulfonylmorpholine 12.5 ± 1.0 1.62 ± 0.04 147.8 ± 3.7
a

All experiments to determine IC50 and AC50 values were run with at least duplicates at each compound dilution, IC50 and AC50 values were averaged when determined in two or more independent experiments.

b

Hill coefficient obtained upon fitting the concentration-response curves.

c

DGC activity of the enzyme-substrate-inhibitor complex.